In advance of the 2018 publication of the paper in the Journal of Alzheimer’s Disease (JAD): ‘Nutritional intervention to prevent Alzheimer’s Disease: potential benefits of xanthophyll carotenoids and omega-3 fatty acids combined’, Dr Howard talked about the events leading up to this discovery.

Background:

Alzheimer’s disease is a modern ailment brought about by people living longer. In 2009, Dr Howard began collaborating with Dr John Nolan and his team at the Nutrition Research Centre of the Waterford Institute of Technology. Together, after nine years of research, they have identified a treatment that may prevent, or at least slow down the onset of, Alzheimer’s disease. Further research and a carefully-monitored clinical trial are now underway to corroborate these initial findings.

Dr Alan Howard has had a distinguished career as a nutritionist for more than 60 years, spanning both academic research and business. He is the founder and chairman of the Howard Foundation which supports both scientific research and philanthropy. The early part of Dr Howard’s career was focussed on tackling problems caused by coronary heart disease and obesity. After retiring from active research, he followed new lines of interest and contacts which brought him to consider the nutritional needs of first the eye and then the brain. This research has led to this new, potentially ground-breaking, discovery.

The Interview:

What led you into looking at potential remedies for Alzheimer’s disease?

It followed on from the research I was doing in the early to mid 90’s into diet and coronary heart disease. After I left the Department of Medicine at the University of Cambridge to found a private laboratory at Papworth Hospital near Cambridge, I worked with Professor David Thurnham at the University of Ulster to look into the difference in diets between people in Belfast and Toulouse.

Why Belfast and Toulouse?

We knew that the incidence of coronary heart disease was four times greater in Belfast than Toulouse. Professor Thurnham’s group found that the major difference was that the hydroxy-carotenoids, lutein and zeaxanthin, were twice the concentration in the Toulouse group than in Belfast. This led me to take a greater interest in carotenoids. This research was published in 1996 in the International Journal for Vitamin and Nutrition Research Vol 66 Issue 2 pages 113-118

How did you follow that up?

In 1995, I attended a Gordon Conference in Ventura, California on carotenoids. There I met Dr. Richard Bone and Dr. John Landrum of the Florida International University (‘FIU’) in Miami. They were working on the hydroxy-carotenoids in the macula of the eye. They discovered a new component called mezo-zeaxanthin (‘MZ’), which is similar to lutein. I went to see them in Florida. We agreed that the Howard Foundation would file a patent application on the use of MZ for the prevention and treatment of Age Related Macular Degeneration (AMD) and in 2007 we published their results (in the journal Nutrition and Metabolism) Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin.

So you had international collaboration?

Yes and there was more to follow. At that time there was no availability of MZ and the work came to a halt. However, Bone and Landrum, whilst attending a conference in Australia, met with Jose Torres of Industrial Organica SA (‘IOSA’), a company in Monterrey, Mexico who was making MZ from heating lutein with sodium hydroxide. As a result the Howard Foundation came to an agreement with IOSA on the use of MZ for increasing macular pigment and potentially preventing Age Related Macular Degeneration.

Bone and Landrum had invented a device called a ‘flicker-photometer’ and were able to show an increase in macular pigment using the IOSA product. The product was marketed as Macushield in Europe and Macuhealth in North America.

So you were now looking at the nutritional needs of the eye. How did that lead to looking into Alzheimers disease?

As is often the case in science, one connection leads to another and turns up a suprising result.

The Howard Foundation had contacted their agent Reed Vordenberg of Detroit, Michigan. He had contacts with Frederic Jouhet, a US citizen emigrated from France to Birmingham, Illinois. Jouhet, a financier, contacted a colleague, Dr. David Segal, an ophthalmologist. They formed a company to develop Richard Bone’s flicker-photometer. Over many years they continued to develop their products and I kept in touch.

In 2007, I attended the ARVO conference in Fort Lauderdale, Florida for those interested in optics. Segel and Jouhet had gone to the meeting to discuss trials of the flicker-photometer with Dr. Stephen Beatty and Dr John Nolan of the Waterford Institute of Technology. I decided not to continue with MZ and Macuhealth myself but was interested in the work being done by Beatty and Nolan.

Beatty and Nolan continued their research work in Waterford which led to a number of scientific publications on the efficacy of the three carotenoids (Lutein, Zeaxanthin and Meso-zeaxanthin). Nolan pointed out that the brain contains large amounts of hydroxy-carotenoids and proposed a project to analyse the blood of patients with Alzheimer’s disease (“AD”) and to measure macular pigment in the eye. I agreed with this investigation but it took one year to obtain ethical permission.

By 2010, Nolan found that the blood of those suffering from AD contained less hydroxy-carotenoids than normal subjects, and that their levels of macular pigment was much less. Treatment with a supplement containing the three carotenoids increased both the hydroxy-carotonoids in the blood and also the macular pigment. However there was no effect on the AD symptoms and the patients got worse as would be expected if they were not taking a special treatment.

But that wasn’t the end of your research then?

No. In 2014, I suggested that the blood of AD patients should be analysed for their lipid content. Professor Thurnham suggested that they could be analysed by a scientist at the Medical Research Council Nutrition Unit in Cambridge using their mass spectrometer. To complete the circle, this is where I used to work. They kindly agreed and reported that the results were different from normal and further analysis showed that the difference was due to a deficiency of two Omega-3 fatty acids (DHA and EPA).

And what happened next?

In 2015, I then suggested that Nolan have a new group of AD patients treated with the three carotenoids in which the sunflower seed oil was replaced with one gram fish oil containing the high content of DHA. The object of the trial was to see if it was possible to improve the Omega-3 content in the blood of AD sufferers after six months’ treatment. In addition the capsules (two per day) contained 15 mg vitamin E (alpha tocopherol).

What was the result of this trial?

At the end of this trial, the AD patients were given a sufficient number of capsules to last one year or more. In May 2017, I asked Nolan to ask about the status of the AD patients. In July he reported that after 18 months treatment all the 13 patients in the trial were still well and only one had become worse. Their carers reported that in some cases the patients’ memory had also improved.

This must have been very exciting for you?

It certainly was. We decided to write up the results for the Journal of Alzheimer’s Disease (JAD) which we submitted in February 2018 and which is now published in their June issue. This unexpected result suggested that AD was the result of a dietary deficiency of three components: a) the hydroxy-carotenoids: lutein and zeaxanthin, b) DHA (which is present in a high concentration in the brain) and c) vitamin E.

What happens next?

The study we conducted only involved a small number of people and the results were rather surprising. Therefore, a new trial is underway to last three years and with a larger number of people. The trial is called ReMIND. AD patients are given either the above mentioned preparation or a placebo for two years. The results of this trial will be analysed and we intend to publish the new results in 2020 [note that due to the COVID pandemic, the final collection of results have been delayed to the second half of 2021].

This is a very exciting discovery Dr Howard. Thank you for your time.