Nutrition

Pittsburgh, PA and Shiga, Japan - The low rate of atherosclerosis and heart disease in Japanese people may be related to their very high levels of marine-derived omega-3 fatty acids rather than genetic factors, a new study suggests [1].

The study, published in the August 5, 2008 issue of the Journal of the American College of Cardiology (available online July 28), was conducted by a group led by Dr Akira Sekikawa (University of Pittsburgh, PA, and Shiga University of Medical Science, Japan).

They found that compared with white or Japanese American men living in the US, Japanese men living in Japan had twice the blood levels of omega-3 fatty acids-a finding that was independently linked to low levels of atherosclerosis.

"The death rate from coronary heart disease in Japan has always been puzzlingly low. Our study suggests that the very low rates of coronary heart disease among Japanese living in Japan may be due to their lifelong high consumption of fish," Sekikawa said."

Results showed that the Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar higher levels. The Japanese men also had twofold higher levels of marine-derived omega-3 fatty acids than white and Japanese Americans.

In addition, the significant differences between Japanese and American men in multivariable-adjusted IMT and CAC prevalence became nonsignificant after adjustment further for marine-derived omega-3 fatty acids.

July 29, 2008 - The low rate of atherosclerosis and heart disease in Japanese people may be related to their very high levels of marine-derived omega-3 fatty acids rather than genetic factors, a new study suggests [1].

The study, known as Electron-Beam Tomography, Risk Factor Assessment Among Japanese and US Men in the Post-World War II Birth Cohort (ERA JUMP) included 868 randomly selected men aged 40 to 49. Of these, 281 were Japanese men living in Japan; 306 were white men living in the US, and 281 were third- or fourth-generation Japanese American men from Hawaii. All study participants had a physical examination, completed a lifestyle questionnaire, and had blood tests to measure cholesterol levels and levels of omega-3 fatty acids. Atherosclerosis was assessed by measuring carotid intima-medial thickness (IMT) and coronary artery calcification (CAC).

Results showed that the Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar higher levels. The Japanese men also had twofold higher levels of marine-derived omega-3 fatty acids than white and Japanese Americans.

The study, published in the August 5, 2008 issue of the Journal of the American College of Cardiology (available online July 28), was conducted by a group led by Dr Akira Sekikawa (University of Pittsburgh, PA, and Shiga University of Medical Science, Japan).

They found that compared with white or Japanese American men living in the US, Japanese men living in Japan had twice the blood levels of omega-3 fatty acids - a finding that was independently linked to low levels of atherosclerosis.

Intima-media thickness of the carotid artery and the distribution of lipoprotein subclasses in men aged 40 to 49 years between whites in the United States and the Japanese in Japan for the ERA JUMP study.
Sekikawa A, Ueshima H, Sutton-Tyrrell K, Kadowaki T, El-Saed A, Okamura T, Takamiya T, Ueno Y, Evans RW, Nakamura Y, Edmundowicz D, Kashiwagi A, Maegawa H, Kuller LH.
Metabolism. 2008 Feb;57(2):177-82.
PMID: 18191046
doi: 10.1016/j.metabol.2007.08.022.

In men in the post World War II birth cohort, i.e., men aged 40-49, whites in the United States (U.S.) had significantly higher levels of intima-media thickness of the carotid arteries (IMT) than the Japanese in Japan.

The whites had significantly higher levels of large very-low-density-lipoprotein particles and significantly lower levels of large high-density-lipoprotein particles than the Japanese, whereas the two populations had similar levels of small low-density-lipoprotein particles. The two populations had similar associations of IMT with NMR lipoproteins. Adjusting for NMR lipoproteins did not attenuate the significant difference in IMT between the two populations (0.671 ± 0.006 for the whites and 0.618 ± 0.006 mm for the Japanese, P=0.01, mean (standard error)). Differences in the distributions of NMR lipoproteins between the two populations did not explain the higher IMT in the whites.

Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study.
Sekikawa A, Curb JD, Ueshima H, El-Saed A, Kadowaki T, Abbott RD, Evans RW, Rodriguez BL, Okamura T, Sutton-Tyrrell K, Nakamura Y, Masaki K, Edmundowicz D, Kashiwagi A, Willcox BJ, Takamiya T, Mitsunami K, Seto TB, Murata K, White RL, Kuller LH; ERA JUMP (Electron-Beam Tomography, Risk Factor Assessment Among Japanese and U.S. Men in the Post-World War II Birth Cohort) Study Group.
J Am Coll Cardiol. 2008 Aug 5;52(6):417-24.
PMID: 18672160

Conclusions
Very high levels of marine-derived n-3 FAs have anti-atherogenic properties independent of traditional cardiovascular risk factors and may contribute to lower burden of atherosclerosis in Japanese in Japan, which is unlikely due to genetic factors.

"The results of the uniquely-constructed ERA JUMP Study were just released, a fascinating study of the relationship of omega-3 fatty acids to coronary and carotid plaque.

The study adds insight into why the Japanese experience only one third of the heart attacks of Americans, and why Japan occupies the bottom of the list for least heart attacks among all developed countries.

The Electron-Beam Tomography, Risk Factor Assessment Among Japanese and U.S. Men in the Post-World War II Birth Cohort Study (ERA JUMP), a collaborative U.S.-Japanese effort, compared three groups of men:

-- 281 Japanese men living in Japan
-- 306 non-Japanese men living in the U.S. (Pittsburgh, Pennsylvania)
-- 303 Japanese Americans (having both parents Japanese without "ethnic admixture") living in Hawaii.

The last group represents a group that is genetically similar to the group in Japan, but exposed to an American diet and lifestyle.

Three main measures were compared:

-- Blood levels of omega-3 fatty acids, EPA and DHA)
-- Carotid intimal-medial thickness (CIMT, the thickness of the carotid artery lining that can serve as an index of body-wide atherosclerosis)
-- Coronary calcium (heart scan) scores."

"Lipoprotein(a), or Lp(a), is a problem area in coronary plaque reversal.

While our current Track Your Plaque record holder for largest percentage reduction in heart scan score has Lp(a), it remains among the more troublesome lipoprotein patterns.

One unique treatment for Lp(a) is high-dose omega-3 fatty acids from fish oil. While the data are relatively meager, there is one solid study from Lp(a) expert, Dr. Santica Marcovina of the University of Washington, called "The Lugalawa Study."

In this unique set of observations, 1300 members of a Bantu tribe living in Tanzania were studied. What made this population unusual is the fact that two groups of Bantus lived under different circumstances. One group lived on Nyasa Lake (3rd largest lake in Africa and reputed to have the greatest number of species of fish of any lake in the world) and ate large quantities of freshwater fish providing up to 500 mg of omega-3s, EPA and DHA, per day. Another Bantu group lived away from the lake as farmers, eating a pure vegetarian diet without fish. "

"The Japan eicosapentaenoic acid (EPA) Lipid Intervention Study (JELIS) is a clinical trial that all Track Your Plaquers should know about.

This enormous trial followed a simple design:

Japanese men, between 40-75 years, and Japanese postmenopausal women aged <75 250 years mg total cholesterol with />

"Lisa is one of early success stories: a heart scan score of 447 in her early 40's, modest reduction of CT heart scan score three years ago.

However, Lisa had a difficult time locating oil-based vitamin D. There has, in fact, been a national run on vitamin D and I'm told that even manufacturers are scrambling to keep up with the booming demand. So, she bought tablets instead and was taking 3000 units per day.

She came in for a routine check. Lisa's 25-OH-vitamin D3: 17 ng/ml, signifying severe deficiency, the same as if she were taking nothing at all. (Recall that we aim for 50 ng/ml.)

In other words, vitamin D tablets do not work. It is shameful. I see numerous women taking calcium tablets with D--the vitamin D does not work. I've actually seen blood levels of zero on these preparations. "

Multiple Sclerosis Blog
By Julie Stachowiak, Ph.D.,

"Powerful new evidence about the ability of vitamin D to stem a wide range of diseases has brought the prospect of a nationwide programme to prescribe it in Scotland as a dietary supplement significantly closer.

Reports at the weekend suggested that experts were increasingly convinced that the so-called sunshine drug - whose significance was first revealed in detail by The Times last year - could make a difference to the country's appalling health record.

New research suggests that high doses of vitamin D could dramatically cut the relapse rate in people with multiple sclerosis. According to scientists in Canada, more than a third of sufferers taking high levels of supplement

"April 28, 2009 (Seattle) -- High doses of vitamin D dramatically cut the relapse rate in people with multiple sclerosis, a study shows.

Sixteen percent of 25 people with multiple sclerosis (MS) given an average of 14,000 international units (IU) of vitamin D a day for a year suffered relapses, says Jodie Burton, MD, a neurologist at the University of Toronto. In contrast, close to 40% of 24 MS patients who took an average of 1,000 IU a day -- the amount recommended by many MS specialists -- relapsed, she says.

Also, people taking high-dose vitamin D suffered 41% fewer relapses than the year before the study began, compared with 17% of those taking typical doses.

People taking high doses of vitamin D did not suffer any significant side effects, Burton tells WebMD."

Safety of vitamin D3 in adults with multiple sclerosis.
Kimball SM, Ursell MR, O'Connor P, Vieth R.
Am J Clin Nutr. 2007 Sep;86(3):645-51.
PMID: 17823429

Conclusions: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.

"(WebMD) Eating a low-fat vegan diet may be better at managing type 2 diabetes than traditional diets, according to a new study.

Researchers found 43 percent of people with type 2 diabetes who followed a low-fat vegan diet for 22 weeks reduced their need to take medications to manage their disease compared with 26 percent of those who followed the diet recommended by the American Diabetes Association (ADA).

In addition, participants who followed the vegan diet experienced greater reductions in cholesterol levels and weight loss than those on the other diet."

"In 1995 my son received the devastating diagnosis of MS. Having been a research scientist for 30 years, I decided to plunge into the scientific literature for MS to determine the most likely factors which cause MS and to use this information to develop an effective therapy for my son.

Notably, many people are having great success in halting or greatly slowing MS with nutritional strategies; many Testimonials are available. I am most pleased to report that my son remains in excellent health with no MS symptoms.

I discovered abundant scientific evidence that indicates that various nutritional factors potentially play major roles in the onset and progression of MS. Strangely, this information was not being made available to persons with MS by doctors nor by established MS charities."

"This website is about Vitamin D and MS

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS), with an uncertain cause. Colleen Hayes and Donald Achaeson have suggested that insufficient sunlight exposure and chronic viral infections might be unrelated environmental risk factors for MS. These risk factors may act synergistically to enable the pathogenic autoimmune response.

The prevalence of MS is highest where environmental supplies of vitamin D are lowest. Sunshine enables the production of vitamin D3 (VD3) in the skin. Epidemiological studies have shown that higher vitamin D blood levels are associated with lower risk, less relapses and a slower progression of multiple sclerosis. Higher vitamin D levels can be achieved in part by increased oral intake of VD3.

Optimal health requires serum 25 hydroxyvitamin D levels higher than 20 ng/ml (50 nmol/L) P Lips, 40 ng/ml (100 nmol/L) P Heaney or at least 40 ng/ml (100 nmol/L) R Vieth. "

Professor Departments of Nutritional Sciences, Laboratory Medicine, and Pathobiology, Bone and Mineral Laboratory, Pathology and Laboratory Medicine,
University of Toronto, Toronto, Canada M5S 3E2
Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada

"Dr. Jodie Burton is the acting principal investigator (PI) of the dose-escalation trial of oral vitamin D3 with calcium supplementation in patients with multiple sclerosis with Dr. O'Connor. She started the trial as his fellow, while doing an additional 2 years of training in MS specifically after she received her neurology certification. She completed her fellowship training in 2007. Now she is staff doing clinical research and continuing with the vitamin D trial. As of August 2009, she will be Assistant Professor in Neurology in the Department of Clinical Neuroscience in Calgary and at the University of Calgary. She will be part of the MS team there with Dr. Luanne Metz and the MS group.

Please scroll down for an abstract of the trial:
A Phase I/II dose-escalation trial of oral vitamin D3 with calcium supplementation in patients with multiple sclerosis."

Conclusions:
High-dose VD3 (~10 000 IU/day, possibly higher) in MS is safe and tolerable, with evidence of clinical improvement."

Effectiveness and safety of vitamin D in relation to bone health.
Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V.
Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review.
PMID: 18088161

CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Effectiveness and safety of vitamin D in relation to bone health.
Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V.
Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review.
PMID: 18088161