I have been playing around with different recipes for a a year now and have finally found one my kids love! They ate so many of these last night that I had to hide them just so they wouldn't flush.
Here's what you need:
2 Cups of water or 2 cups of juice
2 Packs of powdered drink mix(2 teaspoons)
6 Tablespoons of gelatin
8 Teaspoons of ascorbic acid
2 Teaspoons of sodium bicarb
Pour a little of the water into a separate cup with 8 teaspoons of ascorbic acid and 2 teaspoons of sodium bicarb. Let that fizz.
Heat up the rest of the jwater and mix in 2 packets of a powder flavored beverage. The water does not need come to a boil. Add in 6 tablespoons of gelatin and mix until fully dissolved. Remove from heat and once cooled down enough, add the vitamin c. Mix until well blended. Pour into glass dish and stick in the fridge. Cut into 32 squares that are 1 gram of vitamin c each. Enjoy!
Metabolic Syndrome X (MSX) is a constellation of 5 risk factors that greatly increase one's chances of developing
Type 2 diabetes, heart disease, and stroke. It is not a disease per se, but is rather an indication of a worsening
metabolic environment that paves the way for disease. It is highly important for the student of nutrition or dietetics to
understand this condition since 68,000,000 American's have this condition per the 2006 NHANES III study; roughly
32 % of the population. (2) Those at greatest risk are those over 55 who are sedentary and obese. Smokers and
heavy drinkers are also at greater risk. However, the NHANES study also noted that teens can have this syndrome so it
is certainly not limited to the elderly and middle ages. Also, perhaps more alarmingly, the study noted a 34% increase
in prevalence from 1990-2006 in women ages 20-39. It was much less common in this age group before 1990 and the
increase in prevalence tracks with the increase in obesity rates that the study also notes from that time period.
Defining Metabolic Syndrome X:
Many different groups have put forth varying definitions of what comprises MSX, such as the American Diabetes
Association, the American Heart Society and other such medical groups. I have chosen to use the definition offered
by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), which states that MSX can
be diagnosed upon confirmation of 3 of the 5 symptoms: 1. Obesity as defined as a waist circumference over 40
inches for men and 35 inches for women, 2. Hypertension measuring greater than 135/80 mmHg, 3. Insulin
Resistance measured by a fasting glucose over 100 mg/dl, 4.Fasting triglycerides over 150 mg/dl, 5. Fasting HDL
Cholesterol less than 40 mg/dl for men and 50 mg/dl for women. Some definitions differ as to whether more
emphasis is placed on insulin resistance or obesity but all the definitions included these two factors. It is possible to
be obese and not have any other symptoms of MSX, so it is clear that obesity partnered with insulin resistance is
crucial to the diagnoses. And when one takes a look at the molecular mechanisms that underlie this condition one
can see why. Obesity and insulin resistance together lead to the other three risk factors which in turn worsen the
obesity and insulin resistance. It really becomes a vicious cycle where each risk factor feeds into the next. (1)
Molecular Mechanisms in Metabolic Syndrome.
Insulin resistance is a key component as mentioned above, without which we cannot diagnose MSX, which is
reasonable as the MSX is a strong predictor of developing type 2 diabetes, and is often referred to as
pre-diabetes. The main role of insulin in human metabolism is in the utilization of glucose, where it stimulates the
of glucose into the cells of skeletal muscles and adipose tissue by way of the GLUT 4 glucose transporter. In adipose
tissue insulin inhibits lypolysis and promotes the storage of glucose and thus clears it out of the blood which protects
the body from the negative effects of high blood sugar. Insulin, when bound to the insulin receptor and
phosphorylated by tyrosine kinase, activates two parallel metabolic pathways, the phosphoinositide 3-kinase
(PI3K-Akt) pathway, and the mitogen-activated protein (MAP) kinase pathway. The
PI3-AKt pathway is critical to much of the downstream activity of insulin and is involved in the other risk factors of
MSX as well. This pathway phophorylates endothelial nitric oxide synthase (eNOS), which is critical for endothelial cell
function, and this pathway also activates the GLUT4 transporter. The MAP kinase pathway is also critical for
endothelial function and when stimulated it releases endothelin 1 which leads to vasoconstriction and increase the
risk of atherosclerosis, when not properly balanced by nitric oxide. In insulin resistance the MAP Kinase pathway is not
inhibited, but the PI3-Akt pathway is, which puts them out of balance. Thus we can see that there will be less
eNOS activity and lower levels of nitric oxide to balance out endothelin-1, as well as inhibited GLUT4 activity
leading to a rise in blood sugar levels. The lower levels of nitric oxide also lead to reduced blood
flow which explains the issues that diabetics often develop with circulation to the lower extremities.(1)
Obesity stimulates the release of adipokines such as TNF-alpha and
IL-6 which are inflammatory agents and increase insulin resistance (IR) and oxidative stress. Obesity also
stimulates the renin-angiotension system which contributes to hypertension and IR. The inhibition of the
PI3-Akt pathway is also initiated by obesity, through the release of excess amounts of free fatty acids (FFA's) into
the blood stream. Finally, the benefical adipokine, adiponectin, is suppressed in obesity. Adiponectin serves to
couple insulin with energy production and its suppression leads to IR. (1)
Dyslipidemia in MSX is featured as high triglycerides (TG) , low HDL count, and increased numbers of VLDL. IR and
visceral obesity directly contribute to these risk factors. Insulin suppresses lipolysis as noted above. When IR is
present, lipolysis is increased, leading to excess FFA's which are the substrate for TG production in the liver.
Increased FFA also stabilizes apoB, which is the major component of VLDL cholesterol, increasing its production.
Insulin also is critical in degrading apoB via the
PI3-Akt pathway, but since this pathway is inhibited in IR, apoB and VLDL will rise. IR also suppresses the production
of lipoprotein lipase which mediates VLDL clearance which leads to high TG levels. HDL is reduced due to the high
VLDL levels. The TG in VLDL can be transferred to HDL cholesterol where the liver will prefer it as a good substrate
for hepatic lipase and clear HDL from the blood, leading to reduced levels, which in turn greatly increases the risk of
Endothelial dysfunction, with the combined downstream risks of atherosclerosis and hypertension are the final
mechanism to review. Normal endothelial function is critical to proper blood flow, resisting the developing of arterial
plaques, and proper blood pressure. Phosphorylation of the endothelial nitric oxide synthase (eNOS) enzyme is
critical to endothelial function and many of risk factors of MSX work together to suppress this enzyme and as a result
less nitric oxide is available to maintain endothelial health. Hyperlipidemia, diabetes and atherosclerosis all suppress
eNOS phosphorylation. As mentioned above it is stimulated by the
PI3-Akt pathway and when this pathway is inhibited by insulin resistance phosphorylation cannot occur, or occurs
at a reduced rate. Adiponectin, also increases eNOS phosphorylation, but this is also suppressed by IR. Also as
mentioned above the MAP Kinase pathway is not inhibited by IR and this being out of balance with the
PI3-Akt pathway creates endothelial dysfunction. Obesity contributes to endothelial dysfunction via the deleterious
effects of TNF-alpha, and IL6.
TNF-alpha stimulates lipolysis which increases FFA levels which as discussed above leads to dyslipidemia.
TNF-alpha also activates NADPH oxidase which creates excess superoxide. Leptin resistance, caused by visceral fat
also increases ROS production, leading to greater inflammation and worsening IR. As vasoconstriction occurs, the
blood flow to skeletal muscles is less efficient, which means the muscles can take up less glucose. In this way we can
see that endothelial dysfunction will worsen IR, which in return will further worsen endothelial dysfunction, creating a
ever worsening situation until full-blown diabetes develops.
Nutritional Factors of Metabolic Syndrome X
MSX is more a disorder of over consumption of the wrong things rather than a disease of pure nutritional deficiency
like scurvy or pellagra. There are however a few key nutrients that if deficient greatly increase one's chances of
developing MSX. The first culprit to look at is trans fatty acids (TFA's). These are saturated fatty acids that have been
hydrogenated to be in the trans configuration, meaning with the double bonds to be one side, and therefore to lack
the 'kink' that cis fatty acids have. This makes them lie closer together and to achieve solidity at room temperature as
well as to be able to withstand high cooking temperatures. They were introduced into the American diet through
products like Crisco in the mid 20th century and became ubiquitous in everything from cooking oil to snack cakes.
Research has proven conclusively their deleterious effects and they are not as prevalent on the market as they once
were (in the US and Europe), but one can still find them in many products sold in supermarket shelves . TFA's are
recommended to be no more than 1% of daily energy consumption to avoid health issues. They can occur naturally in
red meat from ruminants, but in small amounts, so it is not difficult to reach the less than 1% goal even if one ate red
meat every day. TFA's contribute directly to the molecular mechanism discussed above. High amounts of dietary
TFA's, meaning amounts over 2% of energy product directly lead to reduced HDL cholesterol, worsening apoB to
apoA1 ratio, and higher triglycerides, as well as decreased LDL particle size. This occurs as TFA's will directly increase
the production of TNF-alpha in obese and even non-obese subjects. They also directly increase
E-selection which leads to vasodialation, and increase visceral fat which contributes to IR. IL6 levels and C reactive
protein levels are also increased. Free Fatty acids will also be increased which will lead to greater triglycerides as
discussed above. (3)
Almost as harmful as TFA's is high fructose corn syrup. In reality, it is simply the high amounts of fructose in the diet
that are the problem, but HCFS is an egregious offender as it is an unnatural substance that delivers higher amounts
of fructose not found in nature. HFCS can contain as much as 90% fructose but most soft drinks use a 55% fructose
solution which represents 42% of caloric sweeteners added to foods and beverages. In 1978 the percentage of HFCS
in food was 16% versus the 42% levels of today. This is also the same time period when obesity and diabetes and
MSX levels were skyrocketing. Like TFA's, HFCS in these amounts directly contribute to the mechanisms of MSX. As
discussed above glucose enters the cell via the GLUT4 transporter. This is mediated by insulin, and the amount of
glucose that can be converted to triglycerides is further moderated by phosphofrucktokinase, and signals satiety to
the brain. Fructose on the other hand enters the cell via the GLUT5 transporter which is not mediated by insulin. It
does not signal satiety to the brain, and this makes it easy to overconsume as millions of teens demonstrate everyday
by consuming a 64 oz Mountain Dew from convenience stores. Once in the cell, aldolase can easily cleave the
molecule to form trioses that participate in triglyceride formation much more efficiently than glucose does, as it is not
regulated by phospofructokinase. Thus we can see that high consumption of HFCS will lead to hypertriglyceremia
which as we have seen earlier leads to insulin resistance. HFCS also stimulates NADPH oxidase which increases ROS
which reduce beta activity in the pancreas and leads to IR. It is also important to note that even in individual who do
not have obesity, or diabetes or hyperlipidemia, HFCS is associated with
non-alcoholic fatty liver disease. This is due to HFCS causing dysregulation of the mitochondria in hepatocytes. (4) This
evidence makes it clear that HFCS is a standalone risk factor for MSX, and I think a more important one than TFA's.
Although TFA's are worse, they are not as ubiquitous in American society as HFCS which is consumed every day by
millions of Americans. (4)
Along with these two dietary factors, there are a few specific nutrient deficiencies that increase the risk of
developing MSX. Lack of vitamin K is one such deficiency. Per the source's review of the NHANES study there is an
inverse relationship with vitamin K levels and lipid dysregulation as well as hypertension, with a p value of .05. HDL
and CRP levels also showed improvement along with hyperglycemia. The researchers don't exactly know the
underlying mechanism of why this is the case. The deficiency of vitamin K is widespread due to the lack of leafy
greens in the standard American diet. (9) The lack of greens also contributes to magnesium deficiency is also
implicated in the development of MSX. The typical American diet is often high in calcium, due to supplementation
or over consumption of dairy foods like milk or cheese. Yet it is much less replete in magnesium unless one eats a
great deal of high magnesium foods like kale or spinach or pumpkins seeds, or supplements. The dietary imbalance
of Mg to Ca leads to an intracellular imbalance, via activation of the
n-methyl aspartate receptor, and this leads to IR due to a worsening effect on glucose metabolism. The key is the ratio.
It was found that diets that were poor in both Mg and Ca had the highest risk, diets with normal CA and low Mg were
at some risk, and diets replete in both Mg and Ca were in the least risk. Supplementing with magnesium makes a
great deal of sense for anyone at risk of MSX. This is a nutrient that will directly increases the risk of MSX in its
absence and reduces the risk when supplemented or consumed in the diet and it should be considered by anyone
who has or is developing MSX. (5) It has also been noted that those with MSX are deficient in vitamins C and E as well
as other antioxidants. Source 10 finds that ''high levels of oxidative stress deplete endogenous and exogenous pools
of antioxidants'' and as we discussed above, there is much oxidative stress associated with metabolic syndrome. (10)
Medical Treatment of MSX.
Medical treatment is focused on managing the symptoms associated with MSX. There is no one drug that will reduce
all the risk factors, unless that were a drug that could help someone lose weight. Insulin resistance can be treated
with oral drugs such as metformin that improve glucose metabolism. If oral drugs aren't successful, then daily insulin
can be injected to maintain blood sugar levels. Hypertension can be treated with calcium channel blocker, ACE
inhibitors, diuretics, or beta blockers. Hyperlipidemia can be treated with statin drugs or drugs that target triglycerides.
There is an overlap between the therapies that doctors would recommend and what a nutritionist might recommend.
Both agree that the first and best therapy is weight loss and improving the diet. Losing just 10% of body weight will
lead to a reduction in all the 5 symptoms. Exercise has been noted to improve HDL cholesterol levels and to reduce
hypertension. Certainly doctors and nutritionist alike will encourage a more nutritious diet that feature reduced HFCS
trans-fats, and less saturated fats. Cessation of smoking is very important for reducing hypertension and lowering
the risks of heart disease. Cessation or reduction of alcohol consumption is also critical to prevent the worsening of
fatty liver which so often accompanies metabolic syndrome. There is also a direct link to alcohol consumption and
insulin resistance and many doctors will stress these common sense lifestyle changes as part of their medical advice.
Dietary Strategies for Metabolic syndrome.
Beyond the basic advice of exercising more and trying to lose weight, there are specific dietary strategies that can be
implemented that will directly improve the markers of metabolic syndrome. The Mediterranean diet is one such
effective strategy. Source 6 concludes that This is a diet that focuses on low saturated fats, low simple carbs and
replacing those calories with calories from mono unsaturated fats such as found in olive oil and nuts, as well as with
PUFA's such as in seeds, nuts and fish. It has been found that " the replacement of carbohydrate and saturated fat
with MUFAs leads to reductions in glucose and blood pressure and to an increase in HDL in patients with diabetes" so
this dietary factor is directly helpful. N-3 and
N-6 PUFA's also have an inverse relationship with heart disease. I was suprised that omega 6 intake was shown to
improve metabolic syndrome directly, as Omega 6 oils have a poor reputation in the press as being inflammatory.
(12) One study found that 30 grams of walnuts per day, which are an excellent source of
alpha-linoleic acid, improved the HDL to LDL ratio, reduced the total cholesterol, and also improved endothelial function.
N-3 PUFA's from fish oil that are high in DHA and EPA are of particular importance. Diets high in fiber have also been
shown to improve insulin resistance and FFA acid levels. Ideally the diet will include indigestible as well as
fermentable fiber and low glycemic starches. The Mediterranean diet is one example where little red meat is eaten,
and instead there is a great deal of fish, nuts, seeds and whole grains. It has been studied and found to a be a
cardioprotective diet as it naturally adheres to what has been discussed above. (6)
When I choose this topic I was really curious as to whether low carb diets such as the Atkins Diet or South Beach diet
would have a positive effect on metabolic syndrome patients. Source 7 is study that I found fascinating that directly
compares the results of a low carb diet vs. a high carb low fat diet such as the USDA Myplate. The study was 12 weeks
in duration, and the focus was directly on the metabolic impact of the diet as measured by bloodwork, on the
markers of metabolic syndrome. The high fat diet used a ratio of carbs/fat/protein of 12:59:28 and the high carb diet
was 56:24:20, but both diets maintained the same caloric intake of 1800 calories. The first observation was that the
high fat dieters lost more weight during the 12 weeks with 19/20 subjects losing greater than 5% of their body weight,
with 9 of them losing 10%. On the high carb diet only 12 subjects lost 5% and none of them lost 10%. Fasting
glucose was improved by 12% on the high fat subjects, and no improvement on the low fat cohort. Fasting insulin was
reduced by 47% vs 17%. These two findings are hugely significant as if the insulin response can be improved this
significantly than the metabolic syndrome is being reversed. Triglycerides improve by 57% on the low carb vs 24% on
the low fat diet. HDL cholesterol is improved by 13% vs 1% and the LDL particle size was also improved on the low
carb diet, no change on the low fat diet. This finding shows a reduction in the risk of athersclerosis. Further reducing
the heart disease risk was the improvement in APOb|APO a1ratio, which has an impact on cholesterol particle size.
Unique to this study was the measuring of serum retinol binding protein 4. This protein has a direct impact on insulin
resistance and it was reduced on the low carb diet and not at all on the low fat diet. This study makes it clear that over
a 12 week period at least there are many metabolic benefits to a low carb high fat diet vs a more traditional diet
approach. The fact that there is so much measurable improvement in the risk factors of MSX suggest this may be an
good alternate approach and I see it as an alternate strategy for a diet like the Mediterranean diet. (7)
Along with diet there are several supplemental strategies that research has supported as being useful either to all the
symptoms of MSX or to one or more of the risk factors. Correcting magnesium and calcium deficiency is of critical
importance as discussed above. Ensuring the RDI of both delivers the best results as noted in source 5:
" Randomized controlled trials have shown that oral Mg supplementation of 250 and 365 mg/d for 3 and 6 months,
respectively, reduced insulin resistance, and Mg supplementation of 382 mg/d for 4 months improved blood
pressure, fasting plasma glucose and TAG" (5) Supplementing with Vitamin K as mentioned above, largely to correct
the deficiency can reduce the risk of MSX. If one cannot afford adequate fish in their diet, or is perhaps concerned
about the mercury content of fish, then supplementing with fish oil is beneficial as source 6 finds that "1 gram of fish
oil taken for a 12 month period was found to reduce TG levels, liver enzymes, liver steatosis, and TNF-alpha."
(6)(11) If one adds Niacin to their N-3 fish oil, there is a synergistic effect on the
APOb|APO-a1 ratio and the rest of the apoliproteins, and it was found to be more beneficial than taking fish oil
by itself. (8) Source 10 looked at antioxidants and recommends that patients with diabetes or
metabolic syndrome increase their intake of C and E in particular. The researchers found that ." The effects of
vitamins C and E have received a great deal of interest. Through effects on oxidation of LDL cholesterol concentration,
leukocyte adhesion, and endothelial function, vitamins C and E may slow atherosclerosis. For example, vitamin
C and E intakes were positively associated with paraoxonase activity." Paraoxonase enzymes have been proven to
be preventative against atherosclerosis and
are anti-oxidative. (10) Earlier we discussed how nitric oxide product is a key risk factor for heart disease and
hypertension and source 13 finds that "
α-Tocopherol enhances NO production, and its supplementation in hypercholesterolemic men and smokers
preserves endothelium-dependent vasorelaxation." and supplementation with a full spectrum
E vitamin is recommend. (13) Source 14 is a
meta anlysis of 13 studies on the effects of Vitamin C on LDL cholesterol, HDL and triglycerides. 500 mg of
supplemental vitamin C per day was found to reduce TG by 20 mg/dl and LDL cholesterol by 7 mg/dl. There was
not significant increase in HDl. (14)
Metabolic syndrome is largely disorder of obesity and insulin resistance especially when combined with
hypertension and dyslipidemia. The consumption of harmful substances increases its risk greatly. It can be reversed
with careful dietary choices. Low carbohydrate diets are of particular note in treating metabolic syndrome.
Supplementation of certain nutrients can reduce the risk of MSX, or control some of the symptoms.
1. Paul L. Huang, A comprehensive definition for metabolic syndrome, Disease Models and Mechanisms. 2009
May-Jun; 2(5-6): 231–237.
2. Arupendra Mozumdar, PHD and Gary Liguori, PHD, Persistent Increase of Prevalence of Metabolic Syndrome
Among U.S. Adults: NHANES III to NHANES 1999–2006 , Diabetes Care 2011 Jan; 34(1): 216-21
3. Renata Micha & Dariush Mozaffarian Trans fatty acids: effects on metabolic syndrome, heart disease and diabetes,
Nature Reviews Endocrinology 5, 335-344 (June 2009
4. Ferder, L., Ferder, M.D. & Inserra, F., The Role of High-Fructose Corn Syrup in Metabolic Syndrome and
Hypertension Curr Hypertens Rep (2010) 12: 105
5. Moore-Schiltz, L., Albert, J.M., Singer, M.E., Swain, J. and Nock, N.L. (2015) ‘Dietary intake of calcium and
magnesium and the metabolic syndrome in the National Health and Nutrition Examination
(NHANES) 2001–2010 data’, British Journal of Nutrition, 114(6), pp. 924–935.
6. Angela M Zivkovic, J Bruce German, and Arun J Sanyal. Comparative review of diets for the metabolic
syndrome: implications for nonalcoholic fatty liver disease The American Journal of Clinical Nutrition , August 2007
vol. 86 no. 2 285-300
7. Jeff S. Volek,, Stephen D. Phinney, Cassandra E. Forssythe, et al. Carbohydrate Restriction has a More
Favorable Impact on the Metabolic Syndrome than a Low Fat Diet. Lipids April 2009, Volume 44, Issue 4, pp 297–309
8. Savinova OV, Fillaus K, Harris WS, Shearer G, Effects of niacin and
omega-3 fatty acids on the apolipoproteins in overweight patients with elevated triglycerides and reduced HDL cholesterol.
9. Pan Y1, Jackson RT. Dietary phylloquinone intakes and metabolic syndrome in US young adults. J Am Coll
Nutr. 2009 Aug;28(4):369-79.
10. Earl S. Ford, Ali H. Mokdad, Wayne H. Giles and David W. Brown The Metabolic
Syndrome and Antioxidant Concentrations Diabetes Sep 2003, 52 (9) 2346-2352
11. Yong-Seok Kim,1,2 Pengcheng Xun,1 and Ka He1 Fish Consumption,
Long-Chain Omega 3 Polyunsaturated Fatty Acid Intake and Risk of Metabolic Syndrome: A
Meta-Analysis Nutrients. 2015 Apr; 7(4): 2085–2100. Published online 2015 Mar 24
12. Mauno Vanhala*, Juha Saltevo, Pasi Soininen, Hannu Kautiainen, Antti J. Kangas,Mika
Ala-Korpela and Pekka Mäntyselkä Serum
Omega-6 Polyunsaturated Fatty Acids and the Metabolic Syndrome: A Longitudinal
Population-based Cohort Study Am. J. Epidemiol. (2012) 176 (3):253-260.
13. Pankaj Mathur MD,Zufeng Ding PhD,Tom Saldeen MD, PhD,Jawahar L. Mehta MD, PhD Tocopherols in the
Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease, Clinical Cardiology, 14 August
201514. McRae MP. Vitamin C supplementation lowers serum
low-density lipoprotein cholesterol and triglycerides: a
meta-analysis of 13 randomized controlled trials. J Chiropr Med. 2008 Jun;7(2):48-58.