THE CARB-APPROPRIATE CLIFF HARVEY PHD - A MONTHLY RESEARCH REVIEW BY
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
THE
CARB-APPROPRIATE
REVIEW
A MONTHLY RESEARCH REVIEW BY
CLIFF HARVEY PHD
Volume 2 | Issue 3 | March 2020
w w w. c l i f f h a r v e y. c o m
CARB-APPROPRIATE RESEARCH REVIEW
ABOUT CLIFF
Cliff Harvey PhD is an author, clinician, and researcher.
He was one of the first clinical nutritionists to begin
working with ketogenic and low-carb diets, way back in
the 1990s and is also considered a pioneer in the area of
mind-body integrative healthcare.
Cliff's early post-graduate work was in mind-body
healthcare, while his master's research focussed on the
use of medium-chain triglycerides to mitigate 'keto-flu'
and encourage faster induction of nutritional ketosis.
His doctoral thesis continued to investigate keto-flu and
ketogenesis, and the effects of different types of low-carbohydrate diets along with the
individualisation of dietary prescription and how 'carbohydrate tolerance' varies from person-
to-person.
He is a former world champion strength athlete, submission grappler, and author of several
best-selling books, including The Carbohydrate Appropriate Diet, Carb-Appropriate 101, Time Rich
Cash Optional and The Credo.
www.cliffharvey.com
Amazon | Facebook | Twitter | YouTube | Instagram
CARB-APPROPRIATE RESEARCH REVIEW THIS MONTH How to Optimise Brain Health & Reduce the Risk of Age-Relative cognitive decline.................... 1 What are ‘neurodegenerative disorders’? ..................................................................................... 2 What causes cognitive decline?...................................................................................................... 2 How can I improve my brain health and reduce my risk of cognitive decline? .......................... 2 Exercise the brain and the body .................................................................................................... 2 Get enough sleep ............................................................................................................................ 3 Eat a healthy diet based on natural, unrefined foods ................................................................. 3 Increased fruits and vegetables ..................................................................................................... 3 Vitamin C .......................................................................................................................................... 3 Omega 3 fats ................................................................................................................................... 3 Coffee and tea ................................................................................................................................. 4 Multivitamin/Multimineral ............................................................................................................. 4 Medium-chain triglycerides ............................................................................................................ 4 Lion’s Mane mushroom .................................................................................................................. 4 Other supplements indicated for cognitive decline ..................................................................... 5 Can a Keto diet improve cognition and prevent cognitive decline? ............................................ 5 Ketone Bodies ................................................................................................................................. 5 Ketogenic Diets, Ketosis and the Brain ......................................................................................... 6 Why do Ketones Have these Effects on the Brain? ...................................................................... 7 Reduced inflammation ................................................................................................................... 7 Reduced accumulation of malformed proteins and plaques...................................................... 7 Improved fuelling ............................................................................................................................ 7 Reduced excitotoxicity and neurotoxicity ..................................................................................... 8 Neurogenesis .................................................................................................................................. 8 What does this all mean? ............................................................................................................... 8 All About: Nootropics ......................................................................................................................... 9 Purported common nootropics ................................................................................................... 10 Acetylcholine precursors .............................................................................................................. 10
CARB-APPROPRIATE RESEARCH REVIEW Acetyl-L-carnitine........................................................................................................................... 10 Astaxanthin.................................................................................................................................... 11 Bacopa monnieri ........................................................................................................................... 11 Caffeine .......................................................................................................................................... 11 Other constituents from tea ........................................................................................................ 12 Ginkgo biloba ................................................................................................................................ 12 Ginseng .......................................................................................................................................... 12 Ginseng/Ginkgo combination ...................................................................................................... 12 Multivitamins ................................................................................................................................. 13 Sage ................................................................................................................................................ 13 Spearmint ...................................................................................................................................... 13 Lipids and ‘smart fats’ ................................................................................................................... 14 Omega 3 fats ................................................................................................................................. 14 Medium-chain triglycerides .......................................................................................................... 14 Exogenous ketones? ..................................................................................................................... 14 Other ketogenic supplements? .................................................................................................... 15 Fungi............................................................................................................................................... 15 Conclusion ..................................................................................................................................... 15 Research In Brief ............................................................................................................................... 17 Is Evening Primrose Oil worth taking? ......................................................................................... 17 What is the evidence behind the ‘Palaeolithic Ketogenic Diet’? ................................................ 17 Do saunas help detoxification? .................................................................................................... 18 Does the amount of carbohydrate in the diet affect metabolic syndrome risk? ..................... 19 Carbohydrate intake and risk of metabolic syndrome: a dose-response meta-analysis from observational studies ................................................................................................................... 19 Comment ....................................................................................................................................... 20 For New Subscribers......................................................................................................................... 21 References ......................................................................................................................................... 22
CARB-APPROPRIATE RESEARCH REVIEW
HOW TO OPTIMISE BRAIN
HEALTH & REDUCE THE RISK OF
AGE-RELATIVE COGNITIVE
DECLINE
Key Findings:
• A broad range of factors influence brain-health and cognitive decline
• Stress and lack of sleep and exercise are likely to worsen cognitive
decline
• Quality nutrition for unprocessed foods is likely to be preventative for
cognitive decline
• Ketogenic diets offer a potential preventative and treatment option
for neurodegeneration
• Caffeine-containing natural beverages (coffee, tea, cacao) are
neuroprotective and improve cognition
• Many herbs and supplements, including multivitamin/mineral,
Brahmi, sage and related herbs might protect the brain
I
n my clinical practise, we periodically survey our clients on the health conditions or
outcomes that most concern them. In the early years, we would consistently hear that the
biggest concern was quite simply, weight… Now though, weight and body fat have fallen
behind brain health and day-to-day energy as the major concerns for our clients. This is
unsurprising given the rising incidence of neurodegenerative conditions Alzheimer’s,
Parkinson’s, and other diseases that affect the brain and central nervous system.
1CARB-APPROPRIATE RESEARCH REVIEW
What are What causes cognitive
‘neurodegenerative decline?
disorders’? Neurodegenerative disorders and age-
Neurodegeneration is the progressive related cognitive decline are both inherited
damage and destruction of neurons (brain (genetic) and also result from diet and
and nervous systems cells) and/or lifestyle factors. These causes include head
components of those cells. This breakdown injuries, pesticide exposure (Parkinson’s),
of cells results in age-related cognitive hypertension, lack of sleep, and a poor diet,
decline and in more serious cases the along with additional risk factors of
common neurodegenerative disorders; metabolic syndrome and diabetes,
dementias such as Alzheimer’s disease, depression, excessive alcohol use, and
Parkinson’s disease, amyotrophic lateral tobacco use.1
sclerosis (known as Lou Gehrig’s disease)
and Huntington’s disease. According to
How can I improve my
Alzheimer’s Disease International, someone brain health and reduce
in the world develops dementia every 3 my risk of cognitive
seconds. Additionally, over 50 million people
decline?
now live with dementia worldwide and this
number is expected to double every 20 Exercise the brain and the body
years. i The neurodegenerative disorders Lifestyle factors can reduce your risk of
cause progressive disability, incurring a loss cognitive decline and even improve
of cognition, memory, and physical cognitive function. These include engaging
function. Survival times are also typically in leisure and physical activities, playing a
short—for example, the average survival sport, listening to music, and doing brain-
time post-diagnosis for Alzheimer’s disease taxing activities (such as crosswords).1, 2
is only 3-9 years.
Lifestyle factors
Someone in the can reduce your
world develops risk of cognitive
dementia every 3 decline
seconds
People who regularly and actively
participate in a variety of social, cultural, and
intellectual activities that challenge them,
i
https://www.alz.co.uk/research/statistics
2CARB-APPROPRIATE RESEARCH REVIEW
experience lesser cognitive decline, perform dementia. In a review of studies, it was
better on cognitive tests, and are less likely shown that following a Mediterranean diet
to develop neurodegenerative disorders.3 was associated with up to a 48% reduced
Physical activity shows a consistent, yet not risk of dementia, and those with pre-
always significant effect on cognitive decline existing Alzheimer’s disease had a 73%
4-6
and dementia, and it’s likely that the lower mortality risk than those who did not
effects of physical activity alone on cognitive adhere to the diet.9
decline are limited, and that the best effects
Increased fruits and vegetables
come from a combination of physical
activity, improved diet, and regularly Increased intakes of fruit and vegetables are
challenging the brain with new activities.5, 6 associated with both a lower risk of
dementia and slowing rates of age-related
The best effects cognitive decline.1, 10
However, subtype
analysis has demonstrated that this effect is
come from a
restricted to vegetables (and not fruit), with
combination of the strongest effects from cruciferous (like
physical activity, cabbage and broccoli) and green leafy
improved diet, and vegetables.10 It has been further suggested
regularly that a minimum of 3 servings of vegetables
should be consumed daily for this effect.10
challenging the
brain with new
The protective
activities
effect of fruits and
Get enough sleep vegetables is
Not sleeping enough, or poor sleep (i.e. actually limited to
insomnia, and lack of REM sleep) is a risk vegetables…
factor for cognitive decline and dementia.7, 8
It is recommended that people get between Vitamin C
7 and 9 hours of high-quality sleep per Maintaining healthy levels of vitamin C from
night. nutrient-rich foods to avoid a deficiency
(rather than mega-dosing) is also likely to
Eat a healthy diet based on natural,
have a protective function against age-
unrefined foods
related cognitive decline.11
There is a relationship between diet and
cognitive decline and it’s likely that eating a Omega 3 fats
2
diet (such as the Mediterranean diet ) based The omega 3 fats EPA and especially DHA,
mostly on natural, unrefined foods will play an important role in brain development
reduce the risk of cognitive decline and and healthy functioning of the brain and
3CARB-APPROPRIATE RESEARCH REVIEW
central nervous system.12 Omega-3 fats are cognitive and memory performance in trials
13
linked to reduced mental fatigue, and reduced stress and anxiety.27, 28
It is
improved memory and cognition and likely that supporting the nutrient-
1, 14, 15
reduced cognitive decline, reduced sufficiency of the diet could improve long-
rates of depression and improved structural term brain health and reduce cognitive
16, 17
integrity of the brain. Plausible decline.
mechanisms also exist to suggest a
Medium-chain triglycerides
protective role for fish oil in
neurodegeneration in Parkinson’s disease.18 Medium-chain triglycerides (MCT) are
naturally occurring fats found in small
Coffee and tea amounts in dairy products and greater
Caffeine is a well-known cognitive enhancer. amounts in coconut oil. They are also
Evidence shows that caffeine improves commonly used as isolated supplement
attention, vigilance, reaction times, and oils. MCT supplemented diets improve
problem-solving (especially in sleep- mental performance in those with
19, 20
deprived people), and improved mood Alzheimer’s Disease and age-related
29, 30
and reduced fatigue even at low doses of cognitive decline, and a single dose of 20
caffeine-containing beverages (~ 1 cup of g MCT has been shown to improve
20, 21
tea or coffee per day). cognition.31
Caffeine improves Lion’s Mane mushroom
Lion’s mane (Hericium erinaceus) is an edible
mood and reduces
and medicinal mushroom native to North
fatigue, even at America, Europe and Asia belonging to the
low doses tooth fungus group. Lion’s Mane has been
shown to increase ‘Nerve Growth Factor’,32
In addition to its acute effect on mood and
which helps nerves and brain cells to grow
cognition, caffeine-containing beverages
and repair.33-38 Because of this brain-repair
may be protective against cognitive decline
effect, Lion’s Mane is being considered as
and dementia,22 and coffee and tea are also
one of the most promising preventatives for
associated with a reduced incidence of
dementia and cognitive decline.39, 40 It’s also
Parkinson’s disease.23, 24
been demonstrated to significantly reduce
Multivitamin/Multimineral depression and anxiety,34 and to improve
cognitive function.41
Many people do not consume sufficient
essential and secondary nutrients from diet
alone.25, 26
Multinutrient supplements are
suggested to help make up for this nutrient
shortfall and have resulted in improved
4CARB-APPROPRIATE RESEARCH REVIEW
rosmarinic acid, is also common in
Other supplements
other herbs such as rosemary, for
indicated for cognitive which it is named, and thyme).
decline
• Citicoline (an intermediate in the Can a Keto diet improve
creation of phosphatidylcholine cognition and prevent
from choline) is likely to improve
cognitive decline?
cognition in both dementia patients
Ketogenic diets are low enough in
and healthy people.42
carbohydrate and high enough in fat to
• Acetyl-L-carnitine has been shown encourage the creation of ketone bodies in
to reduce fatigue, anxiety and higher than normal amounts (the body
depression, and age-related always produces a small amount of the
42
cognitive defects. ketone bodies). This ketonaemia (the
presence of ketones in the blood) is called
• The traditional ayurvedic herb
nutritional ketosis, which is typically just
Brahmi (Bacopa monnieri) is likely to
called ketosis. Very low carbohydrate
improve cognition, memory, and
ketogenic diets typically result in BOHB
reaction times.43-45
levels of ≥ 0.5 mmol/L,52 and this level is
• The use of Ginkgo is controversial used as the threshold for achieving ketosis
but recent reviews suggest a by nutrition researchers.53-57
plausible role for ginkgo extracts to
reduce cognitive decline (especially A ketogenic diet is
for patients with neuropsychiatric simply a diet very
symptoms).46 low in
• Sage (Salvia officianalis) improves carbohydrate, low-
mood, alertness and attention, to-high in protein,
calmness, and overall cognition,47-50 and high in fat
and is likely to improve brain health
and reduce cognitive decline. Ketone Bodies
The ketone bodies are ‘brain-friendly’ fuels
• Spearmint (Mentha spicata) is
derived from fatty acids and some amino
another common herb with
acids, especially leucine and lysine (which
purported cognitive effects.
can only be converted to ketones, not to
Spearmint extracts have resulted in
glucose). The ketone bodies are
improved cognitive scores in several
acetoacetate, ß-hydroxybutyric acid (BOHB)
studies.51 (Interestingly, one of the
and acetone. While acetoacetate is the
purported ‘active’ chemicals,
5CARB-APPROPRIATE RESEARCH REVIEW
primary ketone body, BOHB functions as improved neuronal fuelling.68, 69
In human
ii
the main fuel ketone. studies the keto-diet has been easily
tolerated by Alzheimer’s patients while
Ketogenic Diets, Ketosis improving cognition and memory
and the Brain performance vs a higher-carbohydrate
70, 71
control group.
The potential role of ketogenic diets for
brain health has been hinted for over a Ketogenic diets also reduce inflammatory
century and keto-diets have been used to damage in Parkinson’s disease.72 In rat
successfully treat childhood epilepsy since models, a ketogenic diet protects
58-61
the 1920s. It is now known that high dopamine-producing neurons of the
carbohydrate diets play a role in the substantia nigra. These neurons are cells
causation of Alzheimer’s Disease and damaged by endotoxicity in Parkinson’s,
cognitive decline, and ketogenic diets offer resulting in the loss of motor and other
62
a potential treatment option. Both calorie- functions and so their protection is a key
restricted diets and ketogenic diets are target of therapy,73 and keto-diets improve
broadly neuroprotective,63 probably due to motor function in rats with Parkinson’s.74
reduced carbohydrate intake (i.e. reduced
glucose-related damage to neurons) and In mouse studies, ketogenic diets reduce
due to the elevation of ketones and the loss of motor neurons on amyotrophic
resultant reductions in oxidation and lateral sclerosis (ALS or ‘Lou Gehrig’s
inflammation, reduced neuronal disease) and reduce muscle wasting.75
hyperexcitability, neuroprotection and Similarly, a ketogenic diet reduces wasting
neurogenesis, and improved fuel efficiency in Huntington’s disease.76
in the brain. 64
Case study evidence is also beginning to
In pilot studies, elevated ketones improve show mood stabilising effects from the
memory in adults with Alzheimer’s and ketogenic diet used to treat type 2 bipolar
reviews of the evidence show a positive role disorder. 77
for the keto-diet in its treatment. Early
research also suggests that keto can reduce
Parkinson’s disease activity.65, 66
Animal studies show benefits for reducing
the plaque deposits that are part of the
damage inflicted by Alzheimer’s,67 along
with improvements in motor function and
Technically BOHB is not a ketone body as the ketone
ii
moiety has been reduced to a hydroxyl group
6CARB-APPROPRIATE RESEARCH REVIEW
affinity for ketone fuels. The entry of long-
Why do Ketones Have
chain fats (the common dietary fats) into the
these Effects on the brain and central nervous system tissue, is
Brain? limited because the use of these fuels by
neurons can cause hypoxia (lack of oxygen)
Reduced inflammation
and cell death. When the blood-brain
β-hydroxybutyrate directly reduces
barrier and cell membranes in the brain are
inflammation by suppressing activation of
damaged by trauma and injury though, or
the NLRP3 inflammasome.78 Interestingly,
by endotoxicity and protein damage, long-
inflammatory messengers like tumour-
chain fats can enter the brain and neurons,
necrosis factor alpha (TNF-α) might reduce
causing further injury. Interestingly
the body’s ability to produce ketones,79 and
astrocytes in the brain and CNS might
so, taking exogenous ketone supplements,
‘scavenge’ some of these fatty acids, to
or MCTs might help the body to reduce
convert them to ketones for use as fuel,
inflammation, while also allowing there to
thus, preventing some of that damage.80
be a better internal environment for
ketogenesis.
Astrocytes in the
Reduced accumulation of brain and CNS
malformed proteins and plaques
‘scavenge’ fatty
Proteins (like tau-protein) in the brain
acids to convert
become distorted (mainly due to
hyperphosphorylation) and accumulate in
them to ketones
the brains of Alzheimer’s patients. These for use as fuel
cause neuronal dysfunction and additional
Glucose in excessive amounts is also
damage to neurons. These malformed and
undesirable, despite it being the main fuel
aggregated proteins are present in most
for the brain. When glucose levels are
people and can cause damage even if that
consistently elevated, there is greater
person does not have Alzheimer’s. These
potential for glycation or damage to proteins
proteins and plaques (β-amyloid) present in
caused when sugars ‘stick’ to proteins,
AD and other neurodegenerations are
which causes them to become
reduced by ketogenic diets/ketones.
dysfunctional. Ketones, on the other hand,
Improved fuelling are able to be used by neurons, without the
Almost all cells, except those lacking raft of negative effects caused by long-chain
mitochondria, such as red blood cells, can fats and excessive carbohydrate intake.
also utilise lipid-derived fatty acids (via β-
Ketones are also protective against the
oxidation) and most cell types (such as
effects of ischemia (loss of blood supply to
neurons and cardiac tissue) have a high
7CARB-APPROPRIATE RESEARCH REVIEW
tissue),81, 82
and cell damage caused by carbohydrate intake and rebound
83
hypoglycaemia. hypoglycaemia (low blood sugar, often
caused by insulin resistance/pre-
Ketones are also diabetes). 84
protective against
Neurogenesis
the effects of Ketones initially increase oxidative stress
ischemia (loss of but a rapid adaptation, along with increased
blood supply to antioxidant activity and reduced
tissue) and cell excitotoxicity also results in increased brain-
derived neurotrophic factor (BDNF).85 This
damage caused
makes it highly likely that ketones can help
by hypoglycaemia
the neurons of the brain to both survive,
Reduced excitotoxicity and and to ‘regrow’ and repair.
neurotoxicity
Ketones improve the GABA to glutamate Ketones can help
ratio. Gamma-aminobutyric acid (GABA) is a the neurons of the
relaxing neurotransmitter, conversely, brain to both
glutamate is an excitatory neurotransmitter.
survive, and to
When there is an imbalance of these (too
‘regrow’ and
much glutamate, and too little GABA),
excitotoxicity occurs. Excitotoxicity refers to repair.
the overstimulation of neurons, especially
by glutamate. This causes an increase in What does this all
calcium uptake into neurons which in turn, mean?
signals the activation of various enzymes Ketones provided by diet or supplements
which in excess, damage DNA, cell can help to support the healthy functioning
membrane, and other structures directly, of the brain and reduce damage to neurons.
and by damaging cell membranes, allow They provide fuel, reduce damage to
additional damage to those cells. This neurons, and reduce the accumulation of
toxicity is implicated in Alzheimer’s, ALS, plaques and proteins implicated in
Parkinson’s, Huntington disease, brain neurodegeneration. Furthermore, they help
injury and concussion, multiple sclerosis, to reduce over-stimulation of the neurons
alcoholism, and drug withdrawal. and improve anxiety.
Excitotoxicity is reduced by ketones and a
ketogenic diet, and worsened by excessive
8CARB-APPROPRIATE RESEARCH REVIEW
ALL ABOUT: NOOTROPICS
Key Findings:
• Caffeine-containing beverages are proven nootropics
• Common herbs like mint, sage, and others are likely to improve
cognition
• Brahmi is a promising cognitive enhancer
• ‘Brain-friendly’ fats like medium-chain triglycerides and omega-3 fats
are beneficial to brain health and function
• Nutrient support from a multi-nutrient can help to support cognition
• Emerging and compelling evidence suggests that mushrooms such as
Lion’s Mane could be potent cognitive enhancers
N
ootropics are drugs, supplements, or foods and beverages that might improve
cognitive functioning, including analytical functions, focus, mood, memory, creativity,
and motivation. They are also known colloquially as smart drugs or cognitive
enhancers (or cognitive ‘boosters’). There are several drugs that are purported to improve
memory and cognition, but increasing attention is being paid to nutritional supplements, herbs,
and mushrooms that might improve mental functioning.
Nootropics fall under the umbrella of
Nootropics are
supplements which, although there may be
some benefits to long-term brain health, are
supplements
primarily designed to improve mental designed to
functioning to a better-than-normal state in improve mental
the short-term, rather than treating a functioning to a
specific pathology or designed to improve
better-than-
function in the future, although commonly
the same ingredients can accomplish
normal state
several of these goals.
9CARB-APPROPRIATE RESEARCH REVIEW
‘mind to muscle link’ because it is the major
Purported common
neurotransmitter involved in signalling the
nootropics muscles of the body to fire. It is also a major
• Acetylcholine precursors (such as neurotransmitter in the brain, and it has
lecithin/phosphatidylcholine and been suggested that it is a key chemical for
citicoline) cognition and mental processes. A
reduction in choline has been observed in
• Acetyl-L-carnitine
the brains of people with Alzheimer’s
• Astaxanthin disease. While phosphatidylcholine from
lecithin has been shown to reliably increase
• Brahmi (Bacopa monnieri)
acetylcholine levels in mice,87 reviews of the
• Caffeine and other compounds from available research (consisting of two
coffee, tea, and cocoa randomised trials) have suggested that
lecithin doesn’t improve cognition in
• Ginkgo biloba
Alzheimer’s patients.42 However, citicoline
• Panax ginseng (an intermediate in the creation of
phosphatidylcholine from choline) is likely
• Multivitamins and minerals
to improve cognition in both dementia
• Sage (Salvia officinalis) patients and healthy people.42
• Spearmint Citicoline is likely
• Lipids (especially DHA from fish oil to improve
and medium-chain triglycerides) cognition in both
• Fungi (especially Hericium erinaceous
dementia patients
– Lion’s Mane) and healthy
people
These nootropics are common either as
foods, supplements, or traditional
medicines with a long history of use, but do
Acetyl-L-carnitine
they work? Acetyl-carnitine is a naturally occurring
substance formed in cells when an acetyl
Acetylcholine precursors group is added to carnitine. Carnitine
Acetylcholine was the first neurotransmitter (created from the amino acid lysine) aids the
identified by scientists and is the most transport of fatty acids into the
abundant neurotransmitter in the mitochondria to be used for energy. Acetyl-
peripheral, autonomic, and enteric nervous carnitine is more easily absorbed and can
systems.86 It is commonly referred to as the cross the blood-brain barrier more easily
than L-carnitine. Acetyl-L-carnitine has been
10CARB-APPROPRIATE RESEARCH REVIEW
shown to reduce fatigue, anxiety and neurotransmitters such as acetylcholine,
depression, and age-related cognitive serotonin, and dopamine.43 In a 2008
defects.42 randomised controlled trial,
160 mg brahmi extract (equivalent to 4 g
Acetyl-L-carnitine dried herb) given to volunteers for 90
has been shown to days, resulting in significant improvements
to memory accuracy.44 A recent (2014) meta-
reduce fatigue,
analysis has summarised the findings from
anxiety and nine existing studies (437 participants),
depression, and showing improved cognition and reaction
age-related times.45
cognitive defects
Caffeine
Astaxanthin Caffeine is a well-known cognitive enhancer.
Reviews of the evidence show that caffeine
Astaxanthin is a red-orange carotenoid
improves attention, vigilance, reaction
found mostly in several species of krill,
times, and problem-solving (especially in
shrimp, algae, and some lichen. Early
sleep-deprived people).19, 20
research suggests that taking an
astaxanthin supplement (6mg astaxanthin
and 10mg sesamin) daily for 12 weeks could
Caffeine improves
improve psychomotor speed and attention,
processing speed in people with mild vigilance, reaction
cognitive impairment.88 times, and
problem-solving
Bacopa monnieri
Bacopa monnieri (water hyssop, brahmi, Large scale reviews of the evidence show
Indian pennywort) is a perennial creeping significant benefits from caffeine for
herb native to India, Australia, Europe, positive mood and lower perceived fatigue.
Africa, Asia, and the Americas. It is a Doses of 12.5 mg up to 400-600 mg (CARB-APPROPRIATE RESEARCH REVIEW
Tea and coffee both produce similar However, more recent (2014 & 2016)
21
benefits to mood and cognition. In reviews suggest a more positive role for
addition to its acute effect on mood and ginkgo extracts for cognition in cognitive
cognition, caffeine-containing beverages decline. In a review of nine trials, it was
may be protective against cognitive decline concluded that ginkgo extract at a dose of
22
and dementia. 240 mg/day is “able to stabilize or slow
decline in cognition, function, and
Other constituents from behaviour” in cognitive impairment and
tea dementia, especially for patients with
neuropsychiatric symptoms.46 In a review of
Tea constituents other than caffeine (L-
21 trials with 2608 patients, Ginkgo biloba
theanine and epigallocatechin gallate)
(in combination with conventional
might also improve cognition. A review of
medicine) was superior in improving
the research in this area suggested that
Alzheimer’s and cognitive impairment
caffeine combined with theanine (as found
scores (at 24 weeks) to control.93
in tea) improved alertness and attention
more than caffeine alone. 89
Ginseng
Ginkgo biloba Ginseng is the root of the Korean Ginseng
(Panax ginseng) plant. This root has a long
Ginkgo (the maidenhair tree) is one of the
history in traditional medicine as an anti-
most ancient species of tree in existence
stress and nervous ‘tonic’ purported to
and has a long history of use in traditional
improve cognition. Studies have suggested
medicine and as a food.
that ginseng might improve cognitive
While the use of Ginkgo is extremely performance,94 and this effect could be
common for cognitive improvements, related to one of the known effects of
several earlier reviews have found no ginseng, which is to help modulate blood
convincing evidence from randomised trials sugar levels.95, 96 While other studies show a
for a meaningful effect on cognition from trend towards improved cognition from
90, 91
ginkgo. A 2009 Cochrane Database ginseng, a lack of consistency among
review concluded, “Ginkgo biloba appears studies reduces the ability to draw
to be safe in use with no excess side effects conclusions from them as a whole. 97
compared with placebo.” But the “evidence
that Ginkgo biloba has predictable and Ginseng/Ginkgo
clinically significant benefit for people with combination
dementia or cognitive impairment is
The use of ginseng and ginkgo in
92
inconsistent and unreliable.”
combination has also been studied in
healthy adults. A dose-dependent effect on
12CARB-APPROPRIATE RESEARCH REVIEW
memory was found (320-960 mg of inflammation, and encouraging neuronal
98
combination vs placebo). repair.47 In studies of healthy people, a
single dose of sage has resulted in improved
Multivitamins memory scores and mood, alertness and
In an 8-week placebo-controlled trial, a attention, calmness, and overall cognition.47,
48
standard over-the-counter multivitamin and
mineral supplement resulted in significant
improvements to contextual recognition In studies of
and memory performance. Similarly, in a healthy people, a
study of school-age children in India, 5 out single dose of
of 7 memory tests were improved
sage has resulted
significantly for those taking a multi- versus
control.27 In a study of healthy women over
in improved
50, it was found that even a single dose of a memory scores
multivitamin reduced depression and and mood,
anxiety, and stress scores several hours alertness and
after supplementation.28
attention,
Sage calmness, and
Sage or Salvia officinalis is a perennial, overall cognition
evergreen herb common in culinary and
Daily use of sage supplements has also
medicinal tradition. Sage contains a large
been studied. A non-randomised, non-
array of compounds that may have
blinded, within-subject study was
cognitive effects including caffeic acid,
conducted for 28 days in 14 healthy people
rosmarinic acid, salvianolic acids,
(18-40 years). At the completion of the
sagecoumarin, lithospermic acid, sagerinic
study, significant improvements were seen
acid, yunnaneic acids, luteolin, apigenin,
for reaction time, cognitive accuracy,
hispidulin, kaempferol, quercetin, a and b-
attention, and short term and working
thujone, camphor, 1,8-cineole, ahumulene,
memory.49 Another trial including cognitive
b-caryophyllene, viridiflorol, carnosic, acid,
function in perimenopausal women found a
ursolic acid, carnosol, and tanshinones.
significant reduction in time for a common
Evidence from in vitro and animal studies
cognitive test (Stroop colour test).50
suggests that these compounds in sage
could improve cognition by reducing
Spearmint
amyloid-β (found in higher amounts on
Spearmint (Mentha spicata) is another
Alzheimer’s and other neurodegenerative
common herb with purported cognitive
disorders), increasing choline, reducing
effects.
anxiety, reducing oxidation and
13CARB-APPROPRIATE RESEARCH REVIEW
Spearmint extracts (>14.5% rosmarinic acid oils. MCT supplemented diets improve
and 24% total phenolic content) have mental performance in those with
resulted in improved cognitive scores in Alzheimer’s Disease and age-related
29, 30
several studies. (Interestingly, rosmarinic cognitive decline, and a single dose of 20
acid is also common in other herbs such as g MCT has been shown to improve
rosemary, for which it is named, and thyme). cognition.31
In a 90-day randomised, double-blind,
placebo-controlled trial, in healthy, active Exogenous ketones?
men and women, 900 mg of spearmint Exogenous ketone supplements provide
extract significantly improved reactive BOHB directly to the body without requiring
51
agility. ketogenesis and without concurrent
elevations in free fatty acids.100 They are
Lipids and ‘smart fats’ considered to be a safe and effective way to
increase ketone body concentrations,101 and
Omega 3 fats
are being studied for their use as potential
The omega 3 fats DHA and EPA play an
treatments for brain injury,102 cancer,103, 104
important role in brain development and
Angelman syndrome,105 and Alzheimer’s
healthy functioning of the brain and central
disease,106 amongst other conditions.
nervous system. DHA, in particular, makes
up the majority of the polyunsaturated fat Exogenous ketone supplements are
content of the brain, comprises over 50% of available as either salts or esters of BOHB.
the plasma membrane of neurons, and is Supplements containing ketone salts are
essential to the functioning of the brain and some combination of sodium-, magnesium-
12
optimising cognition and mood. , calcium or potassium-BOHB, and are
available commercially from several
Omega-3 fats are linked to reduced mental
companies under patent.107 Ketone esters
fatigue,13 improved memory and cognition
have only recently become available for use
and reduced cognitive decline,14, 15 reduced
by the public but are not common at the
rates of depression and improved structural
time of writing and are prohibitively
integrity of the brain.16, 17. Additionally, DHA
expensive. Both ketone esters and salts
improves cognition and behaviour in
elevate BOHB to levels consistent with
children.99
NK.108 Ketone esters increase ketone levels
Medium-chain triglycerides more than equivalent amounts of ketone
Medium-chain triglycerides (MCT) are salts with fewer gastrointestinal symptoms
naturally occurring fats found in small per increment of increase.109
amounts in dairy products and greater Ketone supplements have positive effects
amounts in coconut oil. They are also on anxiety,106 mental performance and
commonly used as isolated supplement memory,106 and reduce inflammation by
14CARB-APPROPRIATE RESEARCH REVIEW
suppressing activation of the NLRP3 ketones without encouraging ketogenesis
78
inflammasome. Ketones show promise for per se.
helping to treat many of the underlying
causes of neurodegeneration cognitive Fungi
decline. Hericium erinaceus (also called lion's mane
mushroom) is an edible and medicinal
Elevated ketones reduce the glutamate-
mushroom native to North America, Europe
GABA imbalance which can commonly
and Asia belonging to the tooth fungus
result in excessive stress and fatigue.110
group. Lion’s Mane has been shown to
They also have been shown to help reduce
increase ‘Nerve Growth Factor’,32 which
the formation and accumulation of brain-
helps nerves and brain cells to grow and
damaging misfolded proteins (such as tau
repair.33-38 Because of this brain-repair
proteins and amyloid-β) seen in
effect, Lion’s Mane is being considered as
neurodegenerative disorders like
one of the most promising preventative
Alzheimer’s disease and dementia.106
treatments for Alzheimer’s Disease and
Animal studies further suggest the utility of
dementia.39, 40 It’s also been demonstrated
ketones to help reduce anxiety,106 and
to significantly reduce depression and
improve learning and memory.106
anxiety after 4 weeks of treatment,34 and to
improve cognitive function.41 Lion’s Mane
Other ketogenic
might also improve physical performance
supplements? by reducing perceived fatigue.111
Many supplements are purported to be
ketogenic (increasing the internal creation Other mushroom types, especially Turkey
of ketones) including leucine, lysine, short- Tail (Trametes versicolor), Cordyceps
chain fatty acids, and medium-chain (Ophiocordyceps sinensis), and Reishi
triglycerides (MCTs). Of these, leucine and (Ganoderma lucidum) are also suggested as
lysine have limited effects on ketone levels. benefiting neural health and cognition.
There is also limited evidence in humans for
the effect of short-chain fats (such as acetic
Conclusion
acid from vinegar, or butyric acid), however, There is no substitute for a good diet,
they are likely to be ketogenic and might be improved sleep, exercise, and living a life of
more so than MCT.54 The most compelling balance, but some supplements can likely
evidence currently exists for the use of MCTs provide a boost to your brainpower and
for ketogenesis, as they reliably and offer other, longer-term health and
consistently increase ketone concentrations cognitive benefits. The strongest evidence
in the blood in a dose-dependent fashion,54 exists for caffeine-containing beverages like
and exogenous ketones reliably increase coffee and tea, and from nutrient-rich herbs
like mint, sage, brahmi, and others such as
15CARB-APPROPRIATE RESEARCH REVIEW
rosemary and thyme. Additionally, from a quality multivitamin/mineral will
emerging benefits from fungi, most help to support cognition, along with
especially Lion’s Mane, but also others like providing brain-friendly lipids; MCTs and the
Turkey Tail (Trametes versicolor) and Reishi omega-3 fats (especially DHA).
(Ganoderma spp.) support a powerful effect
on cognition. Also, ensuring nutrient density
16CARB-APPROPRIATE RESEARCH REVIEW
allowed. In the Palaeolithic ketogenic diet,
RESEARCH IN these obligate carbohydrate foods are
BRIEF removed to bring the diet into line with a
ketogenic diet that is higher in fat and very
low in carbohydrate. It differs from a
Is Evening Primrose Oil worth standard ketogenic diet in that it disallows
taking? dairy, which can be a common allergen,
especially for people with autoimmune or
Reviews of the evidence have shown that inflammatory disorders.
there is little meaningful evidence to
support the use of evening primrose oil [See Is Dairy Inflammatory?]
(EPO) for breast tenderness or
Case studies have shown promising results
dermatitis.112, 113
But one review has
from the paleo-keto approach for Crohn’s
suggested a benefit (versus drugs used for
disease, Gilbert’s syndrome,115 and
treatment) for breast pain. It should be 116
childhood epilepsy.
noted that the studies cited within these
reviews still offer many conflicts.113
Case studies have
There is only limited data on the use of shown promising
primrose oil for schizophrenia but a results for Crohn’s
Cochrane review of this application found
disease, Gilbert’s
no clear effect of EPO supplementation on
schizophrenia.114
syndrome, and
childhood epilepsy
Primrose oil is
In one case, the diet resulted in complete
probably not remission from symptoms of Crohn’s
worth taking disease, which was maintained. 117
In other cases, insulin function was restored
in two patients with type 1 diabetes (a 19
years adult and a child).118, 119
Similarly, a
What is the evidence behind
patient with type 2 diabetes was able to
the ‘Palaeolithic Ketogenic
normalise high blood pressure and
Diet’?
discontinue medications while also
The Palaeolithic ketogenic diet is a version of reducing triglycerides and blood glucose.120
the popular paleo diet. While ‘paleo’ typically It should be noted that the improvement in
involves the removal of processed and glucose and triglycerides were not
unrefined foods, along with grains, legumes, meaningful but the patient had also ceased
and dairy, typically, tubers and fruit are
17CARB-APPROPRIATE RESEARCH REVIEW
medications that were previously helping to As such, it is also highly likely that while
control this. some people will benefit from a paleo-keto
approach, the additional restrictions may
Insulin function not be necessary for many. If a paleo
was restored in approach is working well for you, stick with
it! Similarly, if a keto approach (including
two patients with
dairy) is working for you, there is no need to
type 1 diabetes change. And if you’d like to try a paleo-keto
approach to see how it feels, there’s nothing
The diet has also stabilised disease activity
wrong with that either.
or reduced tumour size in several cancer
patients,121 and resulted in the complete
cessation of cervical intraepithelial
neoplasia (pre-cancer of the cervix) after 26
months on paleo-keto.122 A patient with Do saunas help
rectal cancer following paleo-keto improved
detoxification?
markers and lab findings for 5 months. While saunas are known to be beneficial to
Following this (apparently) adherence health (by inducing ‘heat shock proteins’)
worsened and surgery was needed at 24 and might even aid hypertrophy (muscle
months.123 growth), the evidence for a ‘detox’ effect is
less clear. It is plausible, as the skin is a
While the case study evidence is promising,
major excretory organ and can help the
further randomised controlled trials need to
body to eliminate toxins, and the increased
be performed to compare this diet to
metabolic activity and catabolic processes
others. The cases appear to indicate that
initiated by heat-shock proteins may
people can achieve additional benefits to
amplify this.
either paleo or a keto approach alone by
following a ‘paleo-keto’ approach and this is
likely to be due to two major factors:
research is lacking
although a few
1. When people following keto
eliminate dairy, they may identify an
studies have
underlying intolerance to dairy shown some
proteins
isolated findings
2. When people following paleo go low-
carb, they may achieve benefits of for an effect of
carb-restriction if they are insulin saunas on detox
resistant or have a medical condition
that benefits from carbohydrate
restriction.
18CARB-APPROPRIATE RESEARCH REVIEW
At this stage though, research is lacking Abstract
although a few studies have shown some
Background and Aims
isolated findings for an effect of saunas on
detox, including improved healthy Epidemiological association studies have
questionnaire scores and reduced shown inconsistent findings between
124, 125
neurotoxicity findings. carbohydrate intake and the risk of
metabolic syndrome. Therefore, we aim to
conduct the first dose-response meta-
analysis to investigate this effect.
Does the amount of
carbohydrate in the diet Methods and Results
affect metabolic A systematic search in PubMed and Web of
syndrome risk? Science databases throughout June 01,
2019, together with relevant literature
Carbohydrate intake and risk scrutiny, was performed to identify related
of metabolic syndrome: a studies for inclusion into the study. We
dose-response meta-analysis calculated the odds ratios (ORs) with 95%
from observational studies confidence intervals (CIs) using a random
effect model. Furthermore, subgroup,
Ya-shu Liu, Qi-Jun Wu, Yang Xia, Jia-Yu Zhang,
sensitivity, heterogeneity, and publication
Yu-Ting Jiang, Qing Chang, Yu-Hong Zhao
bias analyses were performed. This meta-
Nutrition, Metabolism and Cardiovascular analysis included 14 cross-sectional and
Diseases four cohort studies, totalling 284,638
participants and 69,554 metabolic
https://doi.org/10.1016/j.numecd.2019.09.0 syndrome cases. The highest versus the
03 lowest carbohydrate intake values were
Highlights associated with increased risk of met.
syndrome (OR: 1.253, 95% CI: 1.147-1.368),
• Carbohydrates intake is associated with moderate heterogeneity (I2=54.5%).
with more likelihood of having
Using dose-response analysis, we found a
metabolic syndrome.
linear association between carbohydrate
• Linear dose-response relationships
were found, with a 2.6% increase in consumption and met. syndrome risk with a
the risk of metabolic syndrome per corresponding OR of 1.026 (95% CI, 1.004-
5% energy intake from 1.048) and with significant heterogeneity
carbohydrates.
(I2=82.0%) at 5% energy from carbohydrate
• Association between carbohydrates
intake. We have found similar results using
intake and risk of metabolic
syndrome appears to be affected by subgroup analyses for major study
region. characteristics and adjustment for
19CARB-APPROPRIATE RESEARCH REVIEW
confounders. Sensitivity analysis further choosing to eat higher carbohydrate diets
enhanced the robustness of the results, and have poorer health habits and might smoke
no publication bias was detected. and drink more, or exercise less. It would be
unlikely if this were the case though.
Conclusion
Typically, those with healthier habits have
Carbohydrate intake is associated with an been more inclined towards a higher
increased risk of developing metabolic carbohydrate intake because that has been
syndrome. Therefore, additional large the prevailing dietary guidance.
prospective cohort studies are warranted to
confirm our findings.126 Typically, those
with healthier
Comment habits have been
In first reading the title of this study, you
more inclined
might be forgiven for thinking, ‘yeah, no
towards a higher
shit…’ but this is important and informative
to the scientific debate around carbs vs fat carbohydrate
and protein. intake because
As a systematic review and meta-analysis, it
that has been the
combines many studies featuring hundreds prevailing dietary
of thousands of participants, and thus, has guidance
significant strength to show robust
associations between dietary inputs and In fact, up until very recently, dietary
health outcomes. But, like all observational guidelines specifically for those with
data, it does suffer from shortcomings as diabetes and metabolic syndrome were
there was no intervention being compared high-fat, low-carbohydrate diets. So, we
to a control or placebo, and no control over most often see in cohort studies, that those
what the participants did and didn’t do. This who tend to eat fewer carbohydrates (and
means that there is a large potential for more meat in particular) are those who are
confounding and other lifestyle factors could change-resistant, and they concomitantly
influence the findings. For example, those have higher rates of smoking, drinking, and
who eat the most carbohydrate might be obesity.
consuming sugary drinks, or other [See this previous issue of CARR]
processed foods that happen to be higher in
carbohydrate content (but are So, the findings of this study seem to be
comparatively nutrient-poor and are stronger than those that suggest we should
independently associated with poor health reduce meat for very small improvements in
outcomes.) It is also possible that those risk (CARB-APPROPRIATE RESEARCH REVIEW
In this research, the highest vs lowest Overall, the ‘state of the nation’ remains
carbohydrate intakes resulted in a 25% generally the same though. Excessive
increased risk of metabolic syndrome and amounts of processed and refined foods
~3% increase in risk per 5% increase in total (which are generally those high in sugar and
energy from carbohydrate (i.e. moving from refined carbohydrate) are the factor most
a 30 to 35% carbohydrate diet). associated with worse health outcomes.
Eating unrefined foods, on the other hand,
is the proven way to reduce disease risk.
FOR NEW SUBSCRIBERS
Remember to check out our previous issues of The Carb-Appropriate Research Review
21CARB-APPROPRIATE RESEARCH REVIEW
REFERENCES
1. Plassman BL, Williams JW, Jr., Burke JR, decline and dementia. Current opinion in
Holsinger T, Benjamin S. Systematic Review: psychiatry. 2014;27(6):478-83.
Factors Associated With Risk for and Possible
Prevention of Cognitive Decline in Later Life. 9. Opie RS, Ralston RA, Walker KZ.
Annals of Internal Medicine. 2010;153(3):182-93. Adherence to a Mediterranean-style diet can
slow the rate of cognitive decline and decrease
2. Klimova B, Valis M, Kuca K. Cognitive the risk of dementia: a systematic review.
decline in normal aging and its prevention: a Nutrition & Dietetics. 2013;70(3):206-17.
review on non-pharmacological lifestyle
strategies. Clinical interventions in aging. 10. Loef M, Walach H. Fruit, vegetables and
2017;12:903-10. prevention of cognitive decline or dementia: A
systematic review of cohort studies. The journal
3. Wajman JR, Mansur LL, Yassuda MS. of nutrition, health & aging. 2012;16(7):626-30.
Lifestyle Patterns as a Modifiable Risk Factor for
Late-life Cognitive Decline: A Narrative Review 11. Harrison FE. A critical review of vitamin C
Regarding Dementia Prevention. Current Aging for the prevention of age-related cognitive
Science. 2018;11(2):90-9. decline and Alzheimer's disease. Journal of
Alzheimer's disease : JAD. 2012;29(4):711-26.
4. Blondell SJ, Hammersley-Mather R,
Veerman JL. Does physical activity prevent 12. Ghasemi Fard S, Wang F, Sinclair AJ,
cognitive decline and dementia?: A systematic Elliott G, Turchini GM. How does high DHA fish
review and meta-analysis of longitudinal oil affect health? A systematic review of
studies. BMC Public Health. 2014;14(1):510. evidence. Critical Reviews in Food Science and
Nutrition. 2018:1-44.
5. Brasure M, Desai P, Davila H, Nelson VA,
Calvert C, Jutkowitz E, et al. Physical Activity 13. Jackson PA, Deary ME, Reay JL, Scholey
Interventions in Preventing Cognitive Decline AB, Kennedy DO. No effect of 12 weeks'
and Alzheimer-Type Dementia: A Systematic supplementation with 1 g DHA-rich or EPA-rich
Review. Annals of Internal Medicine. fish oil on cognitive function or mood in healthy
2018;168(1):30-8. young adults aged 18–35 years. British Journal of
Nutrition. 2012;107(8):1232-43.
6. de Souto Barreto P, Demougeot L, Vellas
B, Rolland Y. Exercise Training for Preventing 14. Lee LK, Shahar S, Chin A-V, Yusoff NAM.
Dementia, Mild Cognitive Impairment, and Docosahexaenoic acid-concentrated fish oil
Clinically Meaningful Cognitive Decline: A supplementation in subjects with mild cognitive
Systematic Review and Meta-analysis. The impairment (MCI): a 12-month randomised,
Journals of Gerontology: Series A. double-blind, placebo-controlled trial.
2017;73(11):1504-11. Psychopharmacology. 2013;225(3):605-12.
7. Xu W, Tan C-C, Zou J-J, Cao X-P, Tan L. 15. Daiello LA, Wellenius G, Ott BR, Buka SL.
Sleep problems and risk of all-cause cognitive Role of supplemental docosahexaenoic acid
decline or dementia: an updated systematic (DHA) for cognition in Alzheimer's disease and
review and meta-analysis. Journal of Neurology, mild cognitive impairment: A systematic
Neurosurgery & Psychiatry. 2019:jnnp- review and meta-analysis of randomized
2019-321896. controlled trials. Alzheimer's & Dementia: The
Journal of the Alzheimer's Association.
8. Spira AP, Chen-Edinboro LP, Wu MN, 2015;11(7):P611.
Yaffe K. Impact of sleep on the risk of cognitive
22You can also read
